Project Summary Peripheral Artery Disease (PAD) affects approximately 10 million patients in the US and is produced by atherosclerotic blockages in the arteries that supply the legs. Traditional treatments, such as revascularization surgery, medication and exercise therapy, do not sufficiently restore walking impairments due to claudication. We propose to use a powered hip exoskeleton to restore mobility. By assisting at the hip, we minimize the risk of skin irritation and ulcers in the lower leg. It is important to individually optimize the pattern of the moment by which an exoskeleton assists during a gait cycle. However, the required protocol durations are problematic for PAD patients. Aim 1 will be to determine the optimal assistance pattern by using a method that we proposed in a recent perspective paper in Science. We propose using real-time measurements of gait variability as an optimization objective for human-in-the-loop optimization. We will use a versatile off-board actuation system that will allow us to test a wide range of timings and magnitudes. Aim 2 will be to determine whether an exoskeleton can increase walking endurances in patients with PAD. We hypothesize that the 6-minute walking time, initial claudication distance and cost of transport will improve. Different exoskeletons are emerging for mobility assistance; however, no extensive human-in-the-loop studies have been conducted in clinical populations. Thus, this application in PAD patients would be innovative. We expect that this methodology can be transferable to other clinical populations with impaired mobility (e.g., the elderly and stroke, Parkinson?s, and cerebral palsy patients) and for optimizing other devices including passive devices and mobile exoskeletons.